Association between Inflammatory Cytokines and Liver Functions in Rheumatoid Arthritis Patients


Background: Rheumatoid arthritis (RA) is associated with abnormal liver tests, and the medications used for RA are often hepatotoxic. Therefore, this study aimed to investigate an association between pro-inflammatory and anti-inflammatory cytokines and liver function tests in RA patients.

Methods: In this descriptive cross-sectional study, 88 RA patients were included, 84 of them were women and 4 men, aged 21–81 years. Serum interleukin-10 (IL-10), interleukin-17 (IL-17), Osteopontin (OPN) were measured and liver function tests were conducted.

Results: The frequency of RA was higher among adults aged >41 years (72 [81.8%]) than young adults aged ≤41 years (16 [18.2%]). RA was more common in women (84 [95.5%]) than in men (4 [4.5%]) – approximately 21:1-fold. Young adults had higher abnormal IL-10 than adult RA patients (OR = 3.72, p-value 0.044). Abnormal IL-17 (OR = 5.67, p-value 0.034) was found to be increased in young-adult RA patients. No association was observed between age and OPN and between the duration of disease and IL-10, IL-17, and OPN. Similarly, no association was noted between the types of treatment and IL-10, IL-17, and OPN, nor between IL-10, IL-17, OPN and liver parameters (AST, ALT, ALP, ALB, TP, and GGT).

Conclusion: Pro-inflammatory and anti-inflammatory cytokines are not associated with abnormal liver functions, as has been demonstrated in RA patients.


rheumatoid arthritis, interleukin, liver function tests, cytokines

[1] Kwan Ho, T. C., Mok, C. C., Cheung, T. T., et al. (2019). Management of rheumatoid arthritis. Clinical Rheumatology, vol. 38, pp. 3331–3350.

[2] Sundbaum, J. K., Eriksson, N., Hallberg, P., et al. (2019). Methotrexate treatment in rheumatoid arthritis and elevated liver enzymes: a long−term follow−up of predictors, surveillance, and outcome in clinical practice. International Journal of Rheumatic Disease, vol. 22, no. 7, pp. 1226–1232.

[3] Conway, R. and Carey, J. (2017). Risk of liver disease in methotrexate treated patients. World Journal of Hepatology, vol. 9, no. 26, pp. 1092–1100.

[4] Rakuomi, O., Go, O., Kamau, E., et al. (2017). Prevalence of abnormal liver function tests in rheumatoid arthritis. African Journal of Rheumatology, vol. 5, no. 1, pp. 70–75.

[5] Shikhpour, E., Noorbakhsh, P., Elnaz, F., et al. (2018). A survey on the role of interleukin 10 in breast cancer. Report of Biochemistry and Molecular Biology, vol. 7, no. 1, pp. 1–10.

[6] Holdsworth, S. R. and Yi, G. P. (2015). Cytokines: names and numbers you should care about. Clinical Journal of the American Society of Nephrology, vol. 10, no. 12, pp. 2243–2254.

[7] Zhang, L. J. and Wang, X. Z. (2006). Interleukin-10 and chronic liver disease. World Journal of Gastroenterology, vol. 12, no. 11, pp. 1681–1685.

[8] Elvira, D., Nasrul, E., Sofyan, Y., et al. (2018). Increased serum levels of interleukin-17 and transforming growth factor in patients with Graves’ disease. Earth and Environmental Science, vol. 125, pp. 1–4.

[9] Mengesha, B. G. and Conti, H. R. (2017). The role of IL-17 in protection against mucosal candida infections. Journal of Fungi, vol. 3, no. 52, pp. 1–12.

[10] Du, W. J., Zhen, J. H., Zeng, Z. Q., et al. (2013). Expressing of Interleukin-17 associated with disease progression and liver fibrosis with hepatitis B virus infection: IL-17 in HBV infection. Diagnostic Pathology, vol. 8, pp. 1–7.

[11] Tan, Z., Qian, X., Jiang, R., et al. (2013). IL-17A play acritical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation. Journal of Immunology, vol. 191, no. 4, pp. 1–11.

[12] Zheng, L., Chu, J., Shi, Y., et al. (2013). Bone marrow-derived stem cells ameliorate hepatic fibrosis by down-regulating interleukin-17. Cell & Bioscience, vol. 3, article 46.

[13] Shi, L., Shi, L., Wang, X., et al. (2018). Regulatory Roles of osteopontin in production of monocyte-origin MCP-1. Cell Transplantation, vol. 27, no. 8, pp. 1185–1194.

[14] Athanasiadous, D., Jiang, W., Goldbaum, D., Saleem, A., et al. (2018). Nanostructure, osteopontin, and mechanical properties of calcitic avian eggshell. Science Advances, vol. 4, no. 3219, pp. 1–13.

[15] Luukkonen, J., Pascual, M. L., Patlaka, C., et al. (2017). Increased amount of phosphorylated proinflammatory osteopontin in rheumatoid arthritis synovia is associated to decreased tartrateresistant acid phosphatase 5B/5A ratio. PLoS ONE, vol. 12, no. 8, pp. 1–15.

[16] Iida, T., Wagatsuma, K., Hirayama, D., and et al. (2018). Is osteopontin a friend or foe of cell apoptosis in inflammatory gastrointestinal and liver diseases? International Journal of Molecular Sciences, vol. 19, no. 7, pp. 1–15.

[17] Dinić, R. B., Rajković, T. S., Zivkovic, V., et al. (2018). Clinical connection between rheumatoid arthritis and liver damage. Rheumatology International, vol. 38, no. 5, pp. 715–724.

[18] Mursal, T., Elbager, S., Fadl Elmola, A., et al. (2016). Differential diagnosis of anemia in rheumatoid arthritis Sudanese patients. World Journal of Pharmaceutical and Medical Research, vol. 2, no. 4, pp. 1–4.

[19] Elsedig, M. I., Elhag, W., Elmak, M. J., et al. (2014). Seroprevalence of human parvovirus B19 antibody among Sudanese patients with rheumatoid arthritis. American Journal of Ethnomedicine, vol. 1, pp. 402–407.

[20] Kobak, S. and Bes, C. (2018). Autumn late: geriatric rheumatoid arthritis. Therapeutic Advances in Musculoskeletal Disease, vol. 10, no. 1, pp. 3–11.

[21] Abdelsalam, S. K., Hashim, N. T., Elsalamabi, E. M., et al. (2011). Periodontal status of rheumatoid arthritis patients in Khartoum state. BMC Research Notes, vol. 4, article 460.

[22] Abd Elazeem, I. M., Mohammed, A. R., and Abdallah, H. N. (2018). Correlation of serum interleukin10 with disease activity and severity in systemic lupus erythematosus. Egyptian Rheumatology and Rehabilitation, vol. 45, no. 1, pp. 1–9.

[23] Akdeniz, S., Akdeniz, O., Sakalli, N., et al. (2018). The relationship between interleukin-17 and osteoporosis in patients with rheumatoid arthritis. Turkish Journal of Osteoporosis, vol. 24, pp. 46–52.

[24] Iwadate, H., Kobayashi, H., Kanno, T., et al. (2013). Plasma osteopontin is correlation with bone resorption marker in rheumatoid arthritis patients. International Journal of Rheumatic Disease, vol. 17, no. 1, pp. 50–56.

[25] Al Zifzaf, S. D., Mokbel, N. A., and Abdelaziz, M. D. (2015). Interleukin-17 in Bechet’s disease: relation with clinical picture and disease activity. Egyptian Rheumatology and Rehabilitation, vol. 42, no. 2, pp. 34–38.

[26] Negera, E., Walker, S., Bobosha, K., et al. (2018). The effects of prednisolone treatment on cytokine expression in patients with Erythema Nodosum Leprosum reactions. Frontiers in Immunology, vol. 9, pp. 1–15.

[27] Noack, M., Ndongo, N., and Miossec, P. (2016). Evaluation of anti-inflammatory effects of steroids and arthritis-related biotherapies in an in vitro coculture model with immune cells and synoviocytes. Frontiers in Immunology, vol. 7, pp. 1–10.